Emerging contaminants such as polar iodinated contrast media (ICMs) are increasingly detected in aquatic environments and remain difficult to remove due to their high solubility, limited sorption affinity, and resilience to conventional treatment. This study presents a comprehensive experimental and modeling investigation aimed at engineering a dually modified montmorillonite (Mt-II) for efficient adsorption of the non-ionic ICM iohexol. Batch and continuous-flow experiments are synergistically integrated with a stochastic multimodel analysis to quantify parameter uncertainty and objectively evaluate competing model formulations using rigorous selection criteria. In batch systems, Mt-II achieves rapid uptake and high removal efficiency (∼93%), outperforming pristine and singly modified clays. Equilibrium data are most plausibly described by the Langmuir and Sips isotherms. On the other hand, kinetic analysis identified external film diffusion as the dominant rate-limiting step, indicating accessible engineered sorption sites. Under flow-through column conditions, Mt-II maintains strong performance, solute breakthrough behavior being governed by mass-transfer regimes dependent on sorbent loading, flow rate, and influent concentration. Stochastic modeling supports a conceptual picture according to which the Thomas and Yan models can reliably capture breakthrough dynamics across diverse operating conditions. Importantly, column capacities remain stable even at elevated influent concentrations, suggesting operation near the practical saturation capacity of the newly engineered material. Density-functional electrostatic potential mapping reveals complementary hydrogen-bonding and π-interaction domains between iohexol and the Mt-II interlayer, providing mechanistic support for macroscopic adsorption behavior. Collectively, these results establish a mechanistically grounded and statistically robust framework elucidating the behavior of tailored amphiphilic organoclays in the presence of pharmaceuticals such as non-ionic ICMs and advancing their potential application in next-generation water treatment technologies.

Ovarian cancer (OC) is one of the leading causes of cancer-related mortality in women, primarily due to the late-stage diagnosis and limited therapeutic efficacy. Three-dimensional (3D) bioprinting enables the fabrication of cell-laden scaffolds that better recapitulate the native spatial organization and may support the investigation of tumor cell behavior. However, high-grade serous ovarian cancer (HG-SOC) cell subtypes remain largely unexplored in bioprinting, and it remains unclear whether a different scaffold composition is required to provide an optimal niche for each subtype. To address these gaps, we developed a 3D bioprinting workflow based on methacrylated gelatin (GelMA) and a hybrid methacrylated hyaluronic acid/methacrylated gelatin formulation (HAGel) to generate constructs containing KURAMOCHI and OVCAR3 HG-SOC cells, alongside SKOV3 as a reference epithelial OC model. Bioink formulations were optimized to achieve reproducible extrusion printing and stable construct formation. Rheological characterization showed a higher storage modulus for HAGel scaffold (approximately 2-fold higher than GelMA), while both formulations remained within a stiffness range suitable for cell culture. GelMA exhibited higher swelling and a broader printability window, whereas HAGel showed reduced water uptake and required more restricted processing conditions to ensure stable bioprinting. Cellular responses were evaluated in terms of viability, proliferation, morphology, and expression of hyaluronic-acid-associated markers (e.g., CD44, MMP-2, and MMP-14). Postprinting viability remained high throughout culture (approximately 80-99% after 14 days), with outcomes depending on both cell line and hydrogel formulation. KURAMOCHI and SKOV3 cells exhibited higher viability and cell density in HAGel, whereas OVCAR3 cells performed better in GelMA, consistent with CD44 expression and MMP trends, reflecting subtype-dependent interactions with the scaffold composition. These findings demonstrate the feasibility of bioprinting HG-SOC cells and show how bioink formulations may contribute to cell-line-dependent response, paving the way for a rational design of constructs for advanced OC in vitro platforms.

Nanogels (NGs) are versatile polymeric nanocarriers with high drug loading capacity and colloidal stability, making them pivotal candidates for targeted biomedical applications. Surface functionalization with biomolecules is essential for selective targeting therapies; however, conventional covalent conjugation can compromise the activity of sensitive ligands (e.g., proteins and antibodies). The His-tag strategy offers a reversible, oriented binding through coordination with transition metal ions, widely used in protein purification, but scarcely explored for polymeric NG decoration. Here, we developed polyallylamine-based NGs via an emulsion-evaporation process. The NG outer layer was functionalized with lysine-conjugated nitrilotriacetic acid to chelate Ni2+ or Co3+ ions, enabling the His-tag strategy. To validate this approach, a His-Rhodamine compound was used as a representative His-tag structure, mimicking potential bioactive ligands or motifs. Our results demonstrate that Co3+ provides superior His-tag grafting density compared to Ni2+, preserving the biocompatibility of the nanoscaffold. The cobalt-complexed NGs were also tested as cisplatin delivery systems, showing enhanced therapeutic performance compared with the administration of the free drug in ovarian cancer cells. Overall, the cobalt-mediated His-tag conjugation proved to be an efficient approach for the noncovalent surface decoration of polymeric NGs, defining a reliable alternative for the functionalization of this type of nanoscaffolds. Owing to the presence of His-tag functionalities in several biomolecules, the proposed strategy can be readily extended to a wide range of His-tag-based species, thus providing a flexible platform for the design of advanced, targeted NGs with improved selectivity and therapeutic potential.

3D printing is emerging as a promising fabrication technique for microfluidic devices. In this work, this technology was exploited in the development of a microfluidic chromatographic column with nominal volume of 54 µL. The microcolumn was packed with a cation exchange resin and characterized, using potassium iodide as a tracer, in terms of porosity (ε = 0.72), plate number, and asymmetry factor (0.8 < AS < 1.8 for flowrates >50 µL/min). To showcase the potential of this microdevice, it was exploited in the characterization of the chromatographic behavior of lysozyme. The measured saturation capacity (q∞= 88.14 g/Lresin at 340 cm/h) was in line with the manufacturer declaration (85-135 g/L at <500 cm/h). In addition, the effect of NaCl at different concentrations on the protein adsorption isotherm was characterized, demonstrating a Langmuir to anti-Langmuir transition at concentrations ≥300 mM. The axial dispersion coefficient was finally determined ( D A X ${{\mathcal{D}}_{AX}}$ = 6.7 · 10-9 m2/s). In this way, the mcirofluidic column allowed to develop a comprehensive mechanistic model describing the transport of lysozyme in the chromatographic medium using only 30 µL of resin and <1 g of protein, addressing the issue of limited availability of biomolecules and streamlining the process development.

Microfluidics is a promising technology for meeting different lab-scale or industrial-based needs. The fabrication of a plethora of devices, including droplet generators, reactors, organs-on-chip, mixers, and separators at the microscale, is rapidly advancing and aimed to overcome the actual limitations in chemical, physical and biomedical fields. This review provides a comprehensive analysis of the current methods and materials used in the fabrication of these systems, with a particular focus on the emerging two-photon polymerization (TPP) 3D printing. Although microfabrication techniques such as soft- and photolithography, micromachining and lamination, have been validated as milestones for the development of microfluidic devices, TPP 3D printing offers unprecedented precision, enabling the creation of complex microstructures with micrometric and nanometric resolution. Despite its potential, the application of TPP in microfluidic device production remains relatively underexplored. A discussion of the fundamental parameters guiding the TPP 3D printing process, the materials used as photoresist and the criteria for their formulations, and the current microfluidic applications is presented. Challenges, criticisms and opportunities associated to TPP are highlighted, showing the unexplored potential of this technology in microfluidics, with the aim of inspiring novel scenarios of applications looking at research and industrial innovation.

The smart combination of controlled drug delivery and magnetic hyperthermia represents a promising approach for potentiating tumor therapeutic treatments, with minimal adverse effects. Indeed, thermoresponsive nano- particles enable an on-demand drug release according to their thermal activation, and the polymeric nano- systems characterized by an Upper Critical Solution Temperature (UCST) are leading candidates for hyperthermia-based strategies. Secondly, heating processes promoted by superparamagnetic nanostructures might enable targeted hyperthermic effects, without interfering on healthy cells. In this work, we combined the advantages of the UCST-type nanoparticles and superparamagnetic iron-based nanoclusters to design innovative nanocomposites for tunable drug release, activated by magnetic hyperthermia. The thermoresponsive nano- particles were obtained via self-assembling of an amphiphilic zwitterionic block copolymer, and the nanoclusters were encapsulated into the polymeric scaffolds via flash nanoprecipitation. The organic and inorganic materials were characterized in terms of composition, size and physicochemical properties, highlighting the potential of the reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization in tuning the copolymer composition and the cloud point of the nanoparticles (investigated range: 30-43 degrees C). We chose 43 degrees C as representative temperature of hyperthermia treatment and we validated our nanocomposites as delivery system for paclitaxel, a chemotherapeutic agent, under alternate magnetic field. The combined effect of magnetic hyperthermia and the polymer thermoresponsive behavior ensured an on-demand drug release when the target temperature was achieved, providing an almost complete drug release in the first two hours. Alternatively, without a magnetically-mediated heating, the nanocomposites retained the payload. This could pave the way for the definition of advanced hyperthermia-mediated therapeutic treatments.

The accurate prediction of drug release kinetics is crucial for designing effective drug delivery formulations. In this context, controlled drug release from hydrogel matrices is a key strategy to enhance therapeutic outcomes while minimizing side effects. In this study, we develop an advanced mathematical model to describe drug release from nanogels, aiming to accurately represent both standard scenarios where the active compound is fully released and cases where diffusion alone is not sufficient to achieve 100% release. The proposed model is based on Fick's diffusion equation but introduces more realistic boundary conditions by eliminating the perfect sink assumption and incorporating a partition coefficient to account for incomplete drug release. The model was applied to six experimental case studies, varying surface charge, pH of the release environment, and nanogel surface functionalization in order to determine the corresponding diffusion coefficient. The results show good agreement with experimental data, providing a consistent interpretation of the release mechanisms observed in the different case studies. This demonstrates the ability of the model to capture the key factors that influence drug release, making it a valuable tool to support the development of new drug delivery systems. By enabling the prediction and optimization of release profiles, the proposed approach can contribute to the design of tailored delivery strategies to achieve improved therapeutic outcomes.

A series of hydroxycarboxylic acids (HAs) with excellent hydrophilic properties are produced from alkali treatment of cellulose-containing materials. The great majority of these hydroxy acids are glucoisosaccharinic acids (GISAs), which are promising starting materials for surfactant synthesis. Amide surfactant mixtures were produced by combining these HAs with primary amines of various alkyl chain lengths, namely, 12, 16 and 18 carbons. The reactions were performed under liquid-assisted grinding (LAG) conditions, a type of mechanochemical synthesis employing small quantities of liquid, water in this case, to favour the homogenization. Yields up to 90% were achieved with the purchased GISAs and up to 85% in terms of GISA-amides using non-purified HA mixtures, regardless of the amine used. Products derived from other HAs were detected as well. The amount of water influenced the efficacy of the mechanical stimuli and, hence, the yield of the reactions. Foam fractionation was employed as an alternative purification method and was effective in enriching the surfactants up to 33% in the described setup. The resulting GISA-amides were able to lower the water surface tension below 27, 31, and 34 mN m-1 for the 12-, 16- and 18-carbon alkyl chains, respectively. The surfactants were also able to form foams and emulsions. Preliminary considerations using data-fitting software and comparison with commercial surfactants (e.g., SPAN (R) 20, MEGA-12, and MEGA 14) showed excellent potential in terms of possible applications and biodegradability.

In this study, we developed a new process integrating glycolysis and methanolysis to depolymerize low-quality polyethylene terephthalate (PET) wastes, particularly post-consumer mixed textiles. PET is first depolymerized with ethylene glycol and a catalyst, i.e. Na2CO3, to produce bis(2-hydroxyethyl) terephthalate (BHET). This is then extracted from the glycolyzed products and a transesterification with methanol is performed, yielding dimethyl terephthalate (DMT). Finally, DMT is recovered from the solution and purified by distillation. The proposed process allows a very low weight ratio between the fibers containing PET and the ethylene glycol used in the glycolysis reaction, thus avoiding a final step of product concentration. Also, BHET dimers and trimers can be recovered together with the monomer, thus increasing the global process yield. Indeed, a global DMT yield up to 77% can be achieved with this hybrid process, which is higher than that of other chemical recycling processes currently applied to textile wastes.

3D bioprinting is rapidly evolving as a transformative technology for constructing biological tissues with precise cell and bioink placement. However, ensuring the quality and viability of bioprinted structures presents significant challenges, highlighting the need for advanced monitoring systems. Our study introduces a space-efficient, non-invasive approach for real-time, in-situ monitoring of cell dispersion in bioprinted constructs. Utilizing a novel in-situ fluorescence microscopy technique, we employ nanoparticles for cell tagging and integrate a compact digital microscope into the bioprinter for layer-by-layer imaging, significantly saving space and weight to make the solution adaptable to any commercial bioprinter. This method enhances in-situ analysis by combining data from the fluorescence system with conventional visible spectrum imaging. The synergy of these datasets provides a detailed method to examine cell dispersion and facilitates continuous monitoring during the bioprinting process. This allows for the immediate identification and correction of irregularities in cell deposition. Our approach aims to advance 3D bioprinting, setting new standards for the reliability and efficiency of bioprinted structures.

Nanogels (NGs) show great potential for innovative therapies due to their capability of reproposing the hydrogels features at the nanoscale. However, conventional batch syntheses exhibit shortcomings that bind the control over the reaction parameters and batch-to-batch reproducibility. Droplet-based microfluidics represents a valuable strategy to overcome these constraints, enabling precise manipulation of fluids/molecules to design nanoscaffolds. Standard microfluidic fabrication methods, such as soft lithography, hot-embossing or molding, require multistep process, and the successful fabrication depends on several factors, including the operator expertise. This work proposes two-photon polymerization (TPP) 3D printing as a straightforward method to produce a microfluidic device for droplet-based synthesis of NGs. The microfluidic platform enables controlled generation of microdroplets (150-80 mu m, with size variation up to 47%), which work as microreactors, allowing modulation of NG dimensions (320-175 nm) and properties, while preserving an extremely low polydispersity (<0.1). NGs composed of polyallylamine and hyaluronic acid are synthesized and evaluated in vitro for cisplatin delivery in ovarian cancer cells. Compared to free drug administration, NG-mediated delivery enhances the therapeutic effect by approximate to 30% after 72 h. This highlights the potential of the nanomaterial in tumoral scenarios and proves the functionality of the TPP-printed microfluidic device in NG droplet-based synthesis.

This study investigates the hydrolytic degradation of polylactic acid (PLA) under different operating conditions to define the microkinetics of polymer decomposition through hydrolysis. The experimental study accounts for the effect of various factors such as temperature, pH, and initial molar mass of the PLA analyzed. High-performance liquid chromatography (HPLC) was adopted to track the concentrations of reagents and degradation products over time. A comprehensive kinetic model was developed, which integrated random chain scission, preferential end-chain scission, and backbiting reactions. The kinetic parameters were derived by fitting experimental data, yielding a generalized expression for the observed rate constant of each reaction as a function of chain length, temperature, and pH. Specifically, the reaction rates were broken down into three distinct contributions: alkaline-catalyzed, uncatalyzed, and acid-catalyzed mechanisms. Ultimately, this functional form is validated across several lactic-acid-based macromolecules, underscoring its applicability to polyesters and polyamides. The resulting mechanistic model exhibits robust predictivity, serving as a valuable tool for the design and optimization of composting processes.

In the last years, 3D bioprinting has gained great interest for the development of advanced models aimed at biological high-throughput studies. Despite the great potentialities, some technical challenges still need to be addressed. Among those is the necessity of creating a bioink formulation that can ensure high batch-to-batch replicability as well as good biocompatibility and mild curing conditions for cell encapsulation. Within this context, polymer formulations capable of reversible sol-gel transitions upon temperature changes, also termed thermoresponsive gelators, may represent an important advancement, enabling cell encapsulation in their liquid state and forming a self-standing 3D model by increasing the temperature. In addition, their possibility of responding to external stimuli, as native tissues are capable of, can pave the way to advanced applications, making these formulations extremely appealing for so-called 4D bioprinting. In this work, we developed a poly(ethylene glycol)-based thermoresponsive gelator undergoing a reversible sol-gel transition at 26 degrees C. We synthesized the polymer via reversible addition-fragmentation chain transfer (RAFT) polymerization. This provided excellent control over the polymer microstructure and in turn the possibility of systematically investigating its role on key physicochemical properties of the gelator, including the thermoresponsive and rheological behaviors. Finally, these formulations were validated in terms of printability through in situ imaging and biocompatibility. Then, they were tested as bioinks in the extrusion-based bioprintingof human umbilical vein endothelial cells, demonstrating their potential in 4D bioprinting applications, behaving as fugitive inks allowing the recovery of the cell component after application of temperature stimulation.

Polyureas spread their portfolio of applications in the last years due to their unique mechanical and chemical properties. However, the scale-up required to sustain this growing interest brings about safety and sustainability concerns. First, the possibility of avoiding the use of isocyanates is compelling. To fill this gap, an innovative isocyanate-free route has been proposed based on the step-growth polymerization of a diazirine with an aliphatic diamine. Still, the selection of an environmentally friendly solvent and the proper understanding of the kinetic mechanism of this polymerization remain as open points to be urgently cleared to favor the adoption of this appealing route. For this reason, the present work pretends to establish a safe solvent for the step-growth polymerization of N,N'-(hexane-1,6-diyl)bis(aziridine-1-carboxamide) based on the evaluation of its Hansen solubility parameters. Then, a systematic kinetic analysis is performed at different stoichiometric ratios of hexamethylenediamine and diaziridine (r) to develop a kinetic model for their co-polymerization, by deriving the rate constant associated with the reaction and its dependence from temperature. With the aid of this model, the polymer microstructure can be reliably predicted and tuned by acting on the process conditions and r, thus expanding the interest in this new class of materials.

Hyperthermia is considered a promising strategy to boost the curative outcome of traditional chemotherapeutic treatments. However, this thermally mediated drug delivery is still affected by important limitations. First, the poor accumulation of the conventional anticancer formulations in the target site limits the bioavailability of the active ingredient and induces off-site effects. In addition, some tumoral scenarios, such as ovarian carcinoma, are characterized by cell thermotolerance, which induces tumoral cells to activate self-protecting mechanisms against high temperatures. To overcome these constraints, we developed thermoresponsive nanoparticles (NPs) with an upper critical solution temperature (UCST) to intracellularly deliver a therapeutic payload and release it on demand through hyperthermia stimulation. These NPs were synthesized via reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization and combine polyzwitterionic stabilizing segments and an oligoester-based biodegradable core. By leveraging the pseudo-living nature of RAFT polymerization, important physicochemical properties of the NPs were controlled and optimized, including their cloud point (Tcp) and size. We have tuned the Tcp of NPs to match the therapeutic needs of hyperthermia treatments at 43 degrees C and tested the nanocarriers in the controlled delivery of paclitaxel, a common anticancer drug. The NPs released almost entirely the encapsulated drug only following 1 h incubation at 43 degrees C, whereas they retained more than 95% of the payload in the physiological environment (37 degrees C), thus demonstrating their efficacy as on-demand drug delivery systems. The administration of drug-loaded NPs to ovarian cancer cells led to therapeutic effects outperforming the conventional administration of non-encapsulated paclitaxel, which highlights the potential of the zwitterionic UCST-type NPs as an innovative hyperthermia-responsive drug delivery system. Through RAFT emulsion polymerization, zwitterionic nanoparticles (NPs) were synthesized as thermally activated drug release systems. Following hyperthermia, drug-loaded NPs outperforms the therapeutic effect of the free drug in ovarian cancer cells.

Bio-based and degradable materials were proposed to challenge the major problem of plastic disposal in the environment. In this context, polyurethane production was re-evaluated, encouraging the search for replacing both petroleum components and highly toxic species. A novel synthesis route is explored in this work, aimed to produce degradable lignin-based polyurethanes. Oligomers from steam-exploded lignin were extracted and used with e-caprolactone (e-CL) to generate a fully bio-based pre-polymer (oligo-grafted-poly(e-CL)), exploiting ringopening polymerization. We have demonstrated that tuning the main reaction parameters, such as e-CL:oligomer and catalyst:e-CL mass ratios, and reaction time, it is possible to obtain different pre-polymers enabling the synthesis of bio-based polyurethanes with variable physicochemical properties. In particular, the oligomeric content modulates the thermal and mechanical properties of the polymer (melting point range: 54-62 degrees C; Young modulus range: 3-7 kPa) and enhances the degradability (up to 13 % wt, in acid environment), highlighting the potential of the material for possible applications.

Environmental concerns are pushing towards more sustainable materials such as degradable or bio-based polymers. 2-methylen-1,3-dioxepane (MDO) is a cyclic ketene acetal monomer that when reacts by radical ring opening polymerization can introduce degradable ester groups in the polymer backbone, but it is generally challenging to incorporate it uniformly with other industrially relevant vinylic monomers such as styrenics, methacrylics, acrylics and vinylics. In this work, we explore the use of butyl crotonate as termonomer to enhance the incorporation of MDO into common industrial monomers taking advantage of the particular reactivities of MDO and crotonate. Styrene is found not suitable for terpolymerization, as it just homopolymerized. With methyl methacrylate, the incorporation of MDO is substantially enhanced due to the presence of BCr, but the terpolymer is not homogeneous, and MDO is primarily incorporated in the closed form, which only partially enhanced the degradability. In the terpolymerization with ethyl acrylate high MDO incorporation is achieved (up to 80 %) and most of it is incorporated in to the open formed (80 %). Therefore, the obtained terpolymer shows complete degradation in 28 days. Last, the terpolymerization of vinyl acetate is the most successful, as almost total conversion of all monomers is achieved in short times, including (100 % conversion of MDO). Furthermore, the obtained terpolymers are highly homogeneous and degraded completely in few hours. The addition of crotonate monomer in formulations where MDO or other cyclic ketene acetal could bring new insights as it is shown that not only the incorporation of cyclic ketene acetals is enhanced but also that it favors the incorporation into the open form, which substantially enhanced the degradability of common polymers produced by radical polymerization.

Plastic waste is one of the world's biggest sources of pollution. Despite the growing trend towards recycling, there are currently no effective technologies to offset the continuous increase in plastic production. Polyesters and polyamides are among the most widely produced single-use plastics, mainly used in the manufacture of textiles and soft drink bottles. Currently, only a small proportion of these polymers can be effectively recycled. The two primary methods employed for this purpose are mechanical and chemical recycling. Presently, mechanical recycling remains the more widely adopted process within the industrial sector. However, the treatment process is limited to a narrow range of waste materials as it is impossible to remove dyes and the mechanical properties deteriorate due to incompatibility between different plastic materials. Another critical limit of this recycling technology is the limited number of recycling loops that can be done due to the thermal degradation that occurs during the extrusion process. The alternative option is chemical recycling, which allows the depolymerization of the original product to recover the monomers directly. The main drawbacks are the long reaction times and the many solvents needed to achieve high-purity products. As a results, chemical recycling is only economically feasible for large companies that can produce the virgin polymer in situ. In this work, a new technology has been patented. This process consists of three main steps. The first one is the distillation-assisted cyclodepolymerization (DA-CDP), introduced as a modification of the CDP process. In this unit, cyclic oligomers together with high molecular weight compounds are produced. Then, after polymer purification, it is possible to achieve the same molecular weight as the initial polymer in less than 30 min, exploiting the ring-opening polymerization (ROP) of the next step.